As we age, our bodies undergo significant changes that can impact our health and increase our risk of neurological disorders. While previous studies have focused on changes in gene expression with aging, this new research delves deeper into the regulatory events that occur after transcription. Using RNA sequencing techniques, scientists examined the transcriptome and translatome of the female mouse hippocampus at different ages to identify alterations in transcript abundance, alternative splicing, and polyadenylation site selection. The findings showed coordinated expression patterns across age, with upregulation of immune-related transcripts and transcripts associated with neuroinflammation. However, some transcripts related to ribonucleoproteins, mitochondrial functions, calcium signaling, and the cell-cycle exhibited discordant profiles, suggesting translational control may be impaired in aging hippocampi. Additionally, increased alternative splicing was observed with age, particularly in functionally-related transcripts involved in synapses/dendrites and RNA-binding proteins. The study also identified minor changes in polyadenylation site selection. Overall, this research provides a valuable resource for understanding the post-transcriptional regulatory landscape of aging in the hippocampus and its potential implications for age-related neurological diseases. For more details, read the full article!

Aging is associated with substantial physiological changes and constitutes a major risk factor for neurological disorders including dementia. Alterations in gene expression upon aging have been extensively studied; however, an in-depth characterization of post-transcriptional regulatory events remains elusive. Here, we profiled the age-related changes of the transcriptome and translatome in the female mouse hippocampus by RNA sequencing of total RNA and polysome preparations at four ages (3-, 6-, 12-, 20-month-old); and we implemented a variety of bioinformatics approaches to unravel alterations in transcript abundance, alternative splicing, and polyadenylation site selection. We observed mostly well-coordinated transcriptome and translatome expression signatures across age including upregulation of transcripts related to immune system processes and neuroinflammation, though transcripts encoding ribonucleoproteins or associated with mitochondrial functions, calcium signaling and the cell-cycle displayed substantial discordant profiles, suggesting translational control associated with age-related deficits in hippocampal-dependent behavior. By contrast, alternative splicing was less preserved, increased with age and was associated with distinct functionally-related transcripts encoding proteins acting at synapses/dendrites, RNA-binding proteins; thereby predicting regulatory roles for RBM3 and CIRBP. Only minor changes in polyadenylation site selection were identified, indicating pivotal 3′-end selection in young adults compared to older groups. Overall, our study provides a comprehensive resource of age-associated post-transcriptional regulatory events in the mouse hippocampus, enabling further examination of the molecular features underlying age-associated neurological diseases.

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